FDA Approves Pfizer RSV Vaccine: URMC Researchers at Center of Development

The US Food & Drug Administration (FDA) is currently reviewing two candidates for a vaccine to prevent respiratory syncytial virus (RSV) in older adults. Researchers from the University of Rochester Medical Center (URMC) are helping lead the development of one of these - a vaccine developed by Pfizer that is detailed in a new study just released in the New England Journal of Medicine (NEJM). Of the four adult RSV vaccine contenders (two under FDA review and two with late phase clinical trials), URMC has been involved in studying three of them.

RSV in older adults has become an increasing concern. There are an estimated 60,000 to 120,000 hospitalizations and 6,000 to 10,000 deaths in adults 65 years or older each year from RSV infection, according to the CDC. Severity of RSV disease can increase with age and comorbidities, such as chronic obstructive pulmonary disease, congestive heart failure, and asthma. Along with COVID and the flu, RSV contributed to the “tripledemic” that has been placing significant strain on the nation’s healthcare system over the last several months.

Previous research has shown that RSV infection does not give a person lasting immunity afterward, and re-infection can happen throughout the lifespan. There is currently no FDA-approved RSV vaccine, but after nearly five decades of vaccine-development efforts, researchers are on the cusp of approval.

Edward Walsh, MD, professor of Medicine, has a long history with Pfizer, working on multiple viral pathogens over the years. This long-standing relationship led to URMC being named a lead site with Walsh as national lead investigator for Pfizer’s phase 3 clinical trial of the RSV vaccine for older adults. In late February, Pfizer presented efficacy and safety data from that clinical trial, available in the NEJM article, to the FDA and the Vaccines and Related Biological Products Advisory Committee (VRBPAC). Walsh was also a lead investigator on the preliminary trials that preceded the phase 3 study.

The promising results show that Pfizer’s vaccine has an efficacy of 66.7 percent to prevent general illness, an efficacy of 85.7 percent to prevent lower respiratory tract infection with three or more symptoms, and an efficacy of 62.1 percent to prevent acute respiratory infection. After presenting full data, the VRBPAC voted in favor of recommending this vaccine to the FDA for approval.

“RSV is the worst disease that nobody knows about,” said co-investigator Ann Falsey, MD, co-director of the UR Vaccine Treatment and Evaluation Unit, a part of the National Institute of Allergy and Infectious Diseases (NIAID) network that was instrumental in studying the first FDA-approved COVID vaccine. “It started to get a lot of press last year after activity surged when COVID public health measures were relaxed, but every year it consistently causes significant numbers of hospitalizations and deaths in older people aged 65 and up.”

Falsey plays a prominent role in RSV vaccine development at URMC. She recently published phase 2 clinical trial results in a New England Journal of Medicine article on the safety and efficacy of a different RSV vaccine for older adults. At another FDA/VRBPAC meeting to review a vaccine candidate from GlaxoSmithKline (GSK), Falsey, while not involved in their clinical trials, presented at the meeting as an expert, testifying to the burden of RSV on the community.

Both Walsh and Falsey have been prominent vaccine researchers for decades. Walsh has been researching RSV since the 1980s, describing epidemiology and clinical characteristics of RSV in adults, with an emphasis on high-risk elderly populations. His early work was the first to identify and characterize the RSV fusion (F) protein, which is used in the current vaccine candidates. Falsey has been involved with clinical and translational vaccine research in respiratory viral infections in adults, including RSV, flu, COVID, parainfluenza, and human metapneumovirus. She is a standing member of the Clinical Studies and Field Research Study Section, and a member of the steering committees for Global Influenza Initiative, Infectious Diseases Society of America, and the American Virology Society.

Walsh and Falsey were at the forefront of COVID vaccine FDA approval. They have taken lessons learned from that time period and applied them to RSV development. “We could conduct bigger clinical trials faster,” said Walsh, “we knew how to have all hands on deck.”

Like most current flu and COVID vaccines, this RSV vaccine does not contain a live virus. Instead, it contains that fusion protein that “sticks out” of RSV’s surface and helps it fuse to host cells, as its name implies. As a backup, this version of the vaccine also contains a small bit of viral DNA that tells cells how to make the RSV fusion protein. RSVpreF is a bivalent recombinant protein subunit vaccine which consists of equal amounts of stabilized prefusion F (preF) antigens from the two major RSV subgroups: RSV A and RSV B

Unlike flu and COVID vaccines, which need to be updated frequently to keep pace with mutating viruses, the Pfizer RSV vaccine candidate has broad immunity. The RSV fusion protein used in the vaccine can protect against many different RSV strains. There are two forms of the protein which changes its shape before and after it has fused with a cell. Previous clinical trials showed that post-fusion based vaccines were insufficient in producing a robust immune response and failed to protect against RSV illness. Subsequent trials showed that pre-fusion vaccines elicited stronger immune responses, so this current vaccine is based on the pre-fusion protein.

An FDA decision is expected in the coming months.